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Ebola hemorrhagic fever

Etiology: - Ebola hemorrhagic fever virus. Epidemiology: 1) disease of primates 2) virus is transmitted to people from wild animals & through human-to-human transmission - contact with blood, secretions, organs or other bodily fluids of infected animals (WHO) - rarely transmitted via an airborne route [19] - virus not transmitted during incubation phase; virus only transmitted when patients are sick [29] - in Ebola-infected macaques, viable virus is detected for 7 days & viral RNA for 10 weeks after death [58] 3) fruit bats of the Pteropodidae family are natural host (WHO) 4) sporadic outbreaks (Central Africa) - 20 cases, 14 deaths in Uganda 2012 [3] - outbreak in Zaire (now the Democratic Republic of Congo [DRC]) [26] 5) 14,383 casess & 8892 laboratory-confirmed cases as of Nov 14, 2014 with 5165 deaths [CDC] - 6535 cases in Liberia, 5335 cases in Sierra Leone - 1st case reported in Mali (Oct 2014) [43] - 528 cases reported in Guinea, Liberia, & Sierra Leone, with 337 deaths (case-fatality rate of 64%) (West Africa) March-June in 2014 [4,6] 6) 5 distinct species (strains) a) Zaire (1976, 1994, 1996, > 300 cases > 80% mortality) b) Sudan (1976, 1979 Sudan, Uganda 50% fatality) c) Tai Forest d) Bundibugyo e) Reston (does not affect humans) f) Ivory Coast mentioned in a reference where Tai Forest & Bundibugyo were not g) 3 different species of Ebolavirus have caused repeated disease outbreaks in Africa [77] 7) new strain of Ebolavirus in Guinea in 2014 [5] 8) CDC urges all US residents to avoid nonessential travel to Liberia, Guinea, & Sierra Leone [7] 9) WHO declares international public health emergency over Ebola outbreak August 2014 [10] 10) scope of Ebola virus (2014) vastly underestimated [12] 11) number of Ebola cases worldwide has nearly reached 5000, including some 2500 fatalities (Sept 2014) - half of the infections occurred Sept 2014 [27] 12) an estimated 550,000 to 1.4 million Ebola infections in Sierra Leone & Liberia could occur by January 2015 ifno action is taken [28] 13) 1st confirmed case of Ebola in U.S., Texas, Sept 30, 2014; man developed symptoms 4 days after returning from Liberia - contacts of patient test negative - children possibly exposed [29] - in home quarantine for family of patient [30] - patient died on Oct. 8, 2014 [33] - healthcare worker providing care for patient with confirmed Ebola virus [34] - 2nd healthcare worker providing care for patient test positive for Ebola virus [36] - both healthcare workers provided care for index patient when he was vomiting & had diarrhea prior to time it was known he had Ebola hemorrhagic fever [36] - 43 contacts of index case declared Ebola-free [40] 14) a doctor in New York City returning from West Africa where working with Doctors without Borders treating Ebola victims tested positive for Ebola Oct 23, 2014 [42] 15) screening for Ebola to start at 5 US airports that receive 94% of persons from Ebola-endemic countries - New York's JFK, Washington Dulles, Chicago's O'Hare, Atlanta's Hartsfield-Jackson, & New Jersey's Newark [33] - persons traveling traveling from Liberia, Sierra Leone, Guinea, & Mali will be subject to 21-day monitoring for Ebola symptoms [CDC] - screening to end for passengers from Mali [55] 16) a nurse's aide in Spain is believed to be the first person to contract the virus outside of Africa - she helped treat a missionary who died of Ebola [33] 17) from July to mid-November 2014, the CDC fielded 650 inquiries from health departments & clinicians regarding people thought to be at risk for Ebola: most were not at high risk [54] 18) Liberia declared Ebola free May 2015 [65] 19) Sierra Leone Ebola free November 2015 [72] 20) end of most recent outbreak of Ebola virus disease in Liberia & all known chains of transmission have been stopped in West Africa [75] 21) death from Ebola reported in Sierra Leone Jan 2016 [76] - end of flareup in Sierra Leone March 2016 [80] 22) Ebola has resurfaced in Guinea (4 deaths) March 2016 [81] - vaccination effort underway [83] 23) Ebola no longer a global public health emergency [82] 24) confirmed case in Liberia April 2016 [84] 25) two confirmed cases of Ebola in the Democratic Republic of Congo April-May 2012, 17 suspected cases, 3 deaths [88] 26) one case of Ebola identified in 2018 in the city of Mbandaka, which lies on the banks of the Congo River in the Democratic Republic of Congo [19] 27) Ebola outbreak in the Democratic Republic of the Congo declared over by WHO July 24, 2018 [91] 28) cluster of Ebola cases reported Democratic Republic of the Congo Aug 1, 2016 [92] 29) case reported in Uganda June 2019 [93] 30) confirmed cases as of June 2019 1990, deaths 1311 [93] 31) Ebola outbreak in the Democratic Republic of the Congo (DRC) declared a Public Health Emergency of International Concern in July 2019 (WHO) [94] - 2500 confirmed or probable cases in the previous year - 140 healthcare workers have been infected; 40 have died - 2 community health workers have been murdered - ongoing unstable security is one of the factors contributing to the outbreak [94] 32) new outbreak of Ebola in West African nation of Guinea & in the Democratic Republic of the Congo (DRC) Feb 2021 (WHO) [96] Pathology: 1) does not illicit much of an immune response 2) necrotic lesions of liver, spleen, kidney 3) end-stage hemorrhage 4) disseminated intravascular coagulation 5) Reston strain preferentially replicates within macrophages & fibroblasts 6) massive cytokine regulation Genetics: - see ebola hemorrhagic fever virus Clinical manifestations: 1) 4-16 days incubation - patients are not infectious during incubation period 2) early manifestations [57] - fever (87%), chills, headache (53%) - myalgia, arthralgia (39%) - anorexia (65%), nausea/vomiting (68%), diarrhea (66%) - abdominal pain (44%), chest pain (37%) 3) late manifestations [57] - dysphagia (33%) - dyspnea (23%) - pharyngitis (22%) - conjuntivitis (21%) - severe hemorrhage, GI, lungs, gingiva (18%) - hiccups (11%) - jaundice (10%) - delirium (13%) - shock 4) survivors recover in 3-5 weeks Laboratory: - Ebola virus RNA - initial test of choice early in the disease [57] - results available in 2-5 hours if diagnostic testing is onsite [57] - false negative may occur within 48-72 hours of symptom onset [57] - retest is indicated - generally negative in serum within 3 weeks of symptom onset [57] - may remain positive in urine & sweat somewhat longer - detected in semen up to 3 months after infection [57] - virus persists in eye after symptoms clear [68] - Ebola virus antigen - less sensitive than Ebola virus RNA [57] - results in 15 minutes [59] - can be used without electricity [59] - Ebola virus serology - Ebola virus IgM in serum detectable several days after appearance of symptoms - Ebola virus IgG in serum detectable several weeks after appearance of symptoms - complete blood count - test to rule out other etiologies - peripheral blood smear for malaria [57] - influenza antigen test [66] - blood cultures for bacterial sepsis [57] - stool culture [57] * safety precautions in handling specimens * Ebola Virus One-Step recalled due in inaccuracy [62] Differential diagnosis: - malaria* - influenza* - other respiratory infections & gastrointestinal infections* * much more common in travelers returning from Liberia as of June 2015 [66,70] Complications: - dehydration is a common cause of death - patients can lose up to 10 L of fluid/day - 71% mortality from Ebola in Guinea [5] - case fatality 70% (Oct 2014) [35] - persistent myalgias & arthralgias - uveitis, arthritis, pancreatitis - persistence of virus in semen (>12 weeks) [57], upt to 9 months [71] & aqueous humor (>9 weeks) [64] - chronic, often debilitating arthralgias (50%) [68] - chronic uveitis, cataracts, in some cases blindness (25%) - persistent neurologic disability - 1/2 of survivors with severe neurologic manifestations [79] including meningitis, hallucinations, or coma - headache, depression, myalgia, weakness, memory loss [79] - chronic headache, fatigue, depression common [68] Management: 1) supportive 2) new guidelines under development by the CDC for healthcare workers treating Ebola-infected patients will mandate personal protective gear that allows no skin to show [39] - WHO personal protective gear recommendations [47] 3) precautions - contact precautions - droplet precautions 4) isolation of suspected cases & infected patients [57] 5) empiric antibiotic coverage with ciprofloxacin [57] - rationale for this is weak, evidence base not provided 6) consider empiric coverage for malaria until ruled out [57] - empiric artesunate-amodiaquine may lower risk of death [74] 7) acetaminophen for fever [57] - evidence base not provided 8) passive transfer of neutralizing antibodies [22] - serum derived from blood of survivors [77] - convalescent plasma does not improve survival [73] 9) experimental therapies - REGN-EB3 & mAb114 more effective (90%) then Ebola monoclonal antibody ZMapp used successfully to treat 2 US Aid workers [15] or remdesivir [95] 10) favipiravir - may reduce mortality in patients with low-to-moderate levels of Ebola virus in the blood (15% vs 30%) - may be useful for post-exposure prophylaxis [69] 11) advanced care available in US & Europe can have a major effect on Ebola-related mortality (37-74% in West Africa) [78] 12) prevention: - Ebola virus vaccines [99] (FDA-approved) [98] induce immunity in humans from day 14 through month 12 [99] - vaccine effective in chimpanzees [23] - multiplicity of different Ebola species causing disease creates difficulties for developing vaccine for humans [77] - intramuscular adenovirus vector vaccine in phase 1 study among 20 healthy adults demonstrated safety & glycoprotein-specific antibody response after 1 dose [52] - case report of post-exposure Ebola virus vaccine effective in exposed US healthcare worker [60] 13) persons who may have been exposed to Ebola virus should not fly on a commercial airline [36] 14) quarantine for asymptomatic health care workers not recommended [44] 15) precautions for sexual transmission during convalescence - no formal evidence exists of sexual transmission, but sexual transmission from convalescent patients cannot be ruled out [61] - seminal fluid may be infectious for at least 3 months after onset of Ebola symptoms - no reports of persistence of live Ebola virus in vaginal secretions of convalescent women - male survivors of Ebola should abstain from sex for 3 months after symptom onset [51] & to consider use of condoms for beyond 3 months [61] - potential case of sexually transmitted Ebola virus [63] - women had unprotected vaginal intercourse with male survivor of Ebola hemorrhagic fever 200 days after onset of his symptom - semen of male showed presence of viral RNA - partial sequencing of viral RNA from the man's semen & the woman's blood showed a close match [63] 16) when symptoms have resolved & Ebola virus RNA in serum is negative, patients are no longer infectious & may return home - exception are: - transmission through semen for > 6 months [57,63] - infectivity of aqueous humor for > 9 weeks [64] 16) as of June 2015, risk of Ebola virus in travelers returning from Liberia is very low * 35 US hospitals designated as Ebola Treatment Centers Dec 2014. [53] Comparative biology: - 7 daily intravenous doses of lipid-encapsulated siRNA resulted in 100% survival of primates given a lethal dose of Marburg virus (also a filovirus) [13] - a single monoclonal antibody (from a long-term Ebola survivor) neutralizes, in vitro, many different strains of Ebola virus - in vivo studies in monkeys demonstrate a protective effect even when administered 5 days after exposure [86] - a small molecule GS-5734 inhibits Ebola replication in vitro - IV once daily for 12 consecutive days, protects monkeys from lethal doses of Ebola even when treatment was started 3 days after exposure [86] Notes: - people traveling from Sierra Leone, Guinea, & Liberia must enter the U.S. through one of 5 designated airports that are set up to screen for Ebola: New York's JFK, Newark, Dulles, Atlanta, and Chicago's O'Hare [41] (Oct 2014)

Related

ebola virus Ebola virus vaccine (Ervebo, rVSV-ZEBOV)

General

viral hemorrhagic fever syndrome; hemorrhagic nephroso-nephritis

Properties

ETIOLOGY: ebola virus

References

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